S100A4 Regulates Macrophage Chemotaxis

Li, Zhong Hua; Dulyaninova, Natalya G.; House, Reniqua P.; Almo, Steven C.; Bresnick, Anne R.

doi:10.1091/mbc.e09-07-0609

Cited by 115 publications

(133 citation statements)

References 92 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…In both models, no effect of S100A4 knockout was observed on reactive astrogliosis (GFAP staining), axonal or oligodendrocyte pathology (NF-200 or tau-1), or neuronal plasticity (GAP-43). Similarly, even though S100A4 has previously been shown to regulate macrophage chemotaxis 32 and thus it might affect post-traumatic inflammation, we did not find difference in the number of microglia/microphages in the sublesion zone (lectin staining). …”

Section: S100a4 Is Upregulated In Brain Injury and Protects Neuronscontrasting

confidence: 65%

The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

Dmytriyeva¹,

Pankratova²,

Owczarek³

et al. 2012

Nat Commun

117

View full text Add to dashboard Cite

Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage and downregulating the neuroprotective protein metallothionein I þ II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor. Our data introduce S100A4 as a therapeutic target in neurodegeneration, and raise the entire S100 family as a potentially important factor in central nervous system injury.

show abstract

Section: S100a4 Is Upregulated In Brain Injury and Protects Neuronscontrasting

confidence: 65%

The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

Dmytriyeva¹,

Pankratova²,

Owczarek³

et al. 2012

Nat Commun

117

View full text Add to dashboard Cite

show abstract

“…Inflammatory cell infiltration, especially that of macrophages, and the levels of cytokines such as IL-6, TNF-α, IL-17 A and MCP-1, were also decreased obviously in S100A4 −/− mice, a finding that is consistent with previous studies that S100A4 recruits macrophages. 44 Furthermore, the NF-κB levels in AOM/DSS-induced colon tissues in S100A4 −/− mice were clearly down-regulated compared with those in WT mice. In vitro, S100A4 could activate the NF-κB signal pathway in macrophages, contributing to the development of CRC by enhancing the proliferation of pre-malignant IECs.…”

Section: Resultsmentioning

confidence: 93%

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis.

show abstract

“…It was recently shown that FSP1 is crucial for proper myosin-IIA assembly and colony-stimulating factor-1 receptor signaling in macrophages and that FSP1 mediates macrophage recruitment and chemotaxis in vivo (34). These data suggest that FSP1 apart from being a marker also has a biological function in macrophages.…”

Section: Discussionmentioning

confidence: 92%

Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver

Österreicher

Penz-Österreicher²,

Grivennikov³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

308

242

View full text Add to dashboard Cite

Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagenproducing myofibroblasts in cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and epithelial to mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagenproducing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including αSMA and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.tumor microenvironment

show abstract

S100A4 Regulates Macrophage Chemotaxis

Cited by 115 publications

References 92 publications

The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver

Contact Info

Product

Resources

About